Haemo-autologous Antegrade Repriming (HAR) as Minimum Impact Perfusion Strategy for Cardiopulmonary Bypass (HARjbm1)

Haemo-autologous Antegrade Repriming (HAR) Clinical Trial for Validation as Minimum Impact Perfusion Strategy in Cardiopulmonary Bypass

Haemo-autologous Antegrade Repriming (HAR) is a procedure based in the combination of evidence proven measures designed to reduce the haemodilution caused by establishing the cardiopulmonary bypass (CPB) during cardiac surgery.

This clinical trial aims to determinate, in one hand, the benefits related to HAR in terms of transfusion, ICU stay, ventilation time, early mortality and complications. In the other hand analyzes the gaseous microemboli (GME) load, comparing the oxygenators venting technology´s efficiency in treatment and control group, and its relation with patient´s neurocognitive status.

Study Overview

• Status: Completed
• Conditions: Embolism, Air; Anemia; Cardiac Disease; Valve Anomalies; Extracorporeal Circulation; Complications; Transfusion; Cognitive; Disorder, Due to General Medical Condition
• Intervention / Treatment: Procedure: HAR

Detailed Description

HAR is a repriming technique based in Retrograde Autologous Priming (RAP), that has been implemented by recently recommended measures in terms of reducing blood transfusions.

The expected clinical benefits are related to hemodilution´s reduction up to only 300ml. The extracorporeal circuit has been reduced to 3/8 inch diameter in both lines, reducing the surface up to 1000ml of dynamic priming.

Vacuum assisted venous drainage (VAVD) allows to empty the venous line after priming and deairing, facilitating the venous flow for CPB initiation.

The antegrade repriming eliminates the maximum amount of crystalloid contained in the circuit, displacing it to a collector bag, by using autologous blood sequestered from the arterial line to the hardshell reservoir.

HAR reduces the CPB hemodilution related to priming from 1500 to 300 ml preventing the usual sudden haemoglobin level reduction occured during every extracorporeal techinque´s establishment.

Our mission is to analyze if HAR can be validated as a safe and effective tool to improve clinical outcomes in cardiac surgery procedures under extracorporeal circulation

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • MU
    • Murcia, MU, Spain, 30011
      • Hospital Clinico Universitario Virgen de la Arrixaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- All patients purposed to undergo elective cardiopulmonary bypass for cardiac valve surgery or other pathologies requiring to open heart chambers.

Exclusion Criteria:

• Urgency and emergency
• Heart transplantations
• Severe cognitive affection
• Active sepsis
• Previous anemia
• Early re-intervention
• Pre-Op extracorporeal membrane oxygenation (ECMO) support
• Hemodynamic unstability during HAR
• Any clinical condition that may force protocol deviation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HAR group; Treated group is exposed to an haematic antegrade autologous repriming of the MiECC CLass IV circuit, reducing the haemodilution related to CPB initiation to a fix amount of 300ml	Procedure: HAR; HAR, the 6 steps procedure that results in 300ml of haemodilution. Step 0: Circuit is primed with 1000ml of crystalloid solution. Step 1: Venous line content is drained to the reservoir. Step 2: arterial srystalloid priming is displaced to the reservoir retrogradely by autologous blood. Step 3: Crystalloid priming is discarded to the collector bag. Step 4: An amount of 300ml of arterial blood is sequestered to the reservoir avoiding the mixture. Step 5: The centrifugal pump and the oxygenator are reprimed with autologous blood displacing the priming and GME to the collector bag. Step 6: CPB is initiated with a low haemodilution of 300ml. Available at: https://zenodo.org/record/4276132#.X7K8AchKgRk; Other Names: Haematic antegrade repriming; Extracorporeal circuit repriming
NO_INTERVENTION: Control Group; Control group is not exposed to HAR. The extracorporeal circuit is a MiECC primed with 1000ml of Isofundin (crystalloid balanced solution) as an standard circuit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transfusion	Blood product consumption during patients hospital stay	1 year
ICU stay	Length of stay at Intensive Care Unit. (days)	1 year
Ventilation time	Hours under mechanical ventilation after surgery	1 year
Complications	Incidence of neurological, respiratory, urinary, cardiologic complications and multiorganic failure	1 year
Mortality	Incidence of death during hospital stay	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Emboli number	Number of total gaseous microemboli delivered by the extracorporeal system to the patient	1 year
Emboli Volume	Volume of total gaseous microemboli delivered by the extracorporeal system to the patient	1 year
Emotional regulation	Evolution of Emotional regulation test results, comparing the variation with the amount of embolic events detected during the extracorporeal procedure. (4-6 months)	6 months after surgery
Visual work memory variation and emboli	Evolution of Visuospatial working memory test results, comparing the variation of the basal status and short term measurements (4-6 months after surgery) with the amount of detected emboli delivered to the patient through the heart-lung machine´s circuit.	6 months after surgery
Executive functions and emboli	Analysis of the clock drawing test variation, comparing basal and short term (4-6 months after surgery) measurements, and the expected relation with the emboli detected during the extracorporeal technique	6 months after surgery
Visual memory and cognitive status evaluation and emboli	Analysis of the variation of cognitive functions using picture tests(comparing basal status and short term evaluation results (4-6 months after surgery) and the amount of emboli delivered to the patient during the cardiopulmonary bypass	6 months after surgery

Collaborators and Investigators

• Sponsor: Juan Blanco Morillo
• Collaborators: Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca
• Investigators: Principal Investigator: Juan B Morillo, M.Sc, IMIB. University Hospital Virgen de la Arrixaca. Murcia

Publications and helpful links

General Publications

• Loor G, Rajeswaran J, Li L, Sabik JF 3rd, Blackstone EH, McCrae KR, Koch CG. The least of 3 evils: exposure to red blood cell transfusion, anemia, or both? J Thorac Cardiovasc Surg. 2013 Dec;146(6):1480-1487.e6. doi: 10.1016/j.jtcvs.2013.06.033. Epub 2013 Aug 30.
• Liu YH, Wang DX, Li LH, Wu XM, Shan GJ, Su Y, Li J, Yu QJ, Shi CX, Huang YN, Sun W. The effects of cardiopulmonary bypass on the number of cerebral microemboli and the incidence of cognitive dysfunction after coronary artery bypass graft surgery. Anesth Analg. 2009 Oct;109(4):1013-22. doi: 10.1213/ane.0b013e3181aed2bb.
• Wang S, Undar A. Vacuum-assisted venous drainage and gaseous microemboli in cardiopulmonary bypass. J Extra Corpor Technol. 2008 Dec;40(4):249-56.
• Evered L, Scott DA, Silbert B, Maruff P. Postoperative cognitive dysfunction is independent of type of surgery and anesthetic. Anesth Analg. 2011 May;112(5):1179-85. doi: 10.1213/ANE.0b013e318215217e. Epub 2011 Apr 7.
• Zhang X, Yan X, Gorman J, Hoffman SN, Zhang L, Boscarino JA. Perioperative hyperglycemia is associated with postoperative neurocognitive disorders after cardiac surgery. Neuropsychiatr Dis Treat. 2014 Feb 19;10:361-70. doi: 10.2147/NDT.S57761. eCollection 2014.
• Segers T, Stehouwer MC, de Somer FMJJ, de Mol BA, Versluis M. Optical verification and in-vitro characterization of two commercially available acoustic bubble counters for cardiopulmonary bypass systems. Perfusion. 2018 Jan;33(1):16-24. doi: 10.1177/0267659117722595. Epub 2017 Aug 2.
• Lazar RM, Pavol MA, Bormann T, Dwyer MG, Kraemer C, White R, Zivadinov R, Wertheimer JC, Thone-Otto A, Ravdin LD, Naugle R, Mechanic-Hamilton D, Garmoe WS, Stringer AY, Bender HA, Kapadia SR, Kodali S, Ghanem A, Linke A, Mehran R, Virmani R, Nazif T, Parhizgar A, Leon MB. Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial. JACC Cardiovasc Interv. 2018 Feb 26;11(4):384-392. doi: 10.1016/j.jcin.2017.10.041. Epub 2018 Feb 1.
• Kurusz M, Butler BD. Bubbles and bypass: an update. Perfusion. 2004;19 Suppl 1:S49-55. doi: 10.1191/0267659104pf720oa.
• Vandewiele K, Bove T, De Somer FM, Dujardin D, Vanackere M, De Smet D, Moerman AT, Bouchez S, Francois K. The effect of retrograde autologous priming volume on haemodilution and transfusion requirements during cardiac surgery. Interact Cardiovasc Thorac Surg. 2013 Jun;16(6):778-83. doi: 10.1093/icvts/ivt085. Epub 2013 Mar 12.
• Spellman T, Rigotti M, Ahmari SE, Fusi S, Gogos JA, Gordon JA. Hippocampal-prefrontal input supports spatial encoding in working memory. Nature. 2015 Jun 18;522(7556):309-14. doi: 10.1038/nature14445. Epub 2015 Jun 8.
• De Somer FM, Vetrano MR, Van Beeck JP, Van Nooten GJ. Extracorporeal bubbles: a word of caution. Interact Cardiovasc Thorac Surg. 2010 Jun;10(6):995-1001. doi: 10.1510/icvts.2009.229088. Epub 2010 Mar 2.
• Basciani R, Kroninger F, Gygax E, Jenni H, Reineke D, Stucki M, Hagenbuch N, Carrel T, Eberle B, Erdoes G. Cerebral Microembolization During Aortic Valve Replacement Using Minimally Invasive or Conventional Extracorporeal Circulation: A Randomized Trial. Artif Organs. 2016 Dec;40(12):E280-E291. doi: 10.1111/aor.12744. Epub 2016 Jun 10.
• Abrahamov D, Levran O, Naparstek S, Refaeli Y, Kaptson S, Abu Salah M, Ishai Y, Sahar G. Blood-Brain Barrier Disruption After Cardiopulmonary Bypass: Diagnosis and Correlation to Cognition. Ann Thorac Surg. 2017 Jul;104(1):161-169. doi: 10.1016/j.athoracsur.2016.10.043. Epub 2017 Feb 10.
• Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Brown JR, Despotis GJ, Hammon JW, Reece TB, Saha SP, Song HK, Clough ER; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; Shore-Lesserson LJ, Goodnough LT, Mazer CD, Shander A, Stafford-Smith M, Waters J; International Consortium for Evidence Based Perfusion; Baker RA, Dickinson TA, FitzGerald DJ, Likosky DS, Shann KG. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011 Mar;91(3):944-82. doi: 10.1016/j.athoracsur.2010.11.078.

Helpful Links

• To assess and compare the effectiveness and costs of Phototest,Screen for dementia (DEM) and cognitive impairment (CI).
• Effect of blood transfusion on long-term survival after cardiac operation - The Annals of Thoracic Surgery
• Effect of blood transfusion on long-term survival after cardiac operation
• Postoperative cognitive dysfunction is receiving increasing attention, particularly cognitive deficits after cardiac surgery

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 15, 2018
• Primary Completion (ACTUAL): September 1, 2019
• Study Completion (ACTUAL): February 9, 2021

Study Registration Dates

• First Submitted: October 18, 2018
• First Submitted That Met QC Criteria: October 24, 2018
• First Posted (ACTUAL): October 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 12, 2021
• Last Update Submitted That Met QC Criteria: February 9, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: cardiopulmonary bypass; perfusion; RAP; Extracorporeal circulation; Retrograde autologous priming; HAR; Gaseous microemboli
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Neurocognitive Disorders; Embolism and Thrombosis; Heart Diseases; Embolism; Embolism, Air; Cognition Disorders
• Other Study ID Numbers: HARjbm1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No